1.Value of 131I SPECT/CT on the re-staging and recurrence risk stratification and its impact on subsequent treatment strategy in post-surgical patients with differentiated thyroid carcinoma
Jinxiong HUANG ; Xiaojiang HE ; Hao YU ; Guibing CHEN ; Weiyi XU ; Lingyun LIN ; Huizhen ZHUANG ; Hua WU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2017;37(9):550-554
Objective To evaluate the role of 131I SPECT/CT in post-surgical re-staging and recurrence risk stratification in patients with DTC and its impact on subsequent treatment strategy.Methods 131I-WBS and 131I SPECT/CT were performed at the same time 5 to 7 d after 131I treatment in 118 patients (33 males,85 females,average age 45 years) with DTC.Difference in the localization and qualitative diagnosis of 131I uptake lesions between 131I-WBS and 131I SPECT/CT were compared.Value of 131I SPECT/CT in the diagnosis of TNM staging,risk stratification and impact on the treatment strategy was evaluated.Paired χ2 test was used for data analysis.Results A total of 509 foci with 131I uptake were detected.131I-WBS found 449 foci with 131I uptake,354 of which (78.84%) were correctly diagnosed.131I SPECT/CT found 509 foci with 131I uptake,and 504(99.02%) were correctly diagnosed.The difference was statistically significant (χ2=21.51,P<0.01).131I-WBS changed the clinical staging in 13 cases with diagnostic accuracy of 5/13.131I SPECT/CT changed the clinical staging in 19 cases and with diagnostic accuracy of 19/19 (χ2=74.41,P<0.01).131I-WBS changed the risk stratification of 13 patients after operation and the accuracy was 5/13,the corresponding data were 22 and 100%(22/22) for 131I SPECT/CT (χ2=74.41,P<0.01).The treatment strategy was changed in 50 patients with 131I SPECT/CT.Conclusions Compared with 131I-WBS,131I SPECT/CT could provide more accurate positioning and qualitative information for 131I treatment and is more accurate in re-staging and risk stratification.
2.Comparison of Efficacy and Safety between Octreotide and Somatostatin in the Treatment of Liver Cirrho-sis and Upper Digestive Tract Hemorrhage:a Meta-analysis
Jianrong ZHUANG ; Peiying ZHENG ; Huizhen GAN
China Pharmacist 2017;20(12):2204-2208
Objective:To compare the efficacy and safety of octreotide and somatostatin in the treatment of liver cirrhosis and up-per digestive tract hemorrhage. Methods:The randomized controlled trails ( RCTs) on the comparison between octreotide and soma-tostatin in the treatment of liver cirrhosis and upper digestive tract hemorrhage were searched from Cochrane Library, PubMed, Med-line, Embase, China National Knowledge Infrastructure(CNKI), VIP China Science and Technology Journal Database and Wanfang database (till February 2017). The randomized controlled trails meeting the inclusion criteria were collected and the quality of included RCTs was assessed according to the Cochrane Collaboration system review, and then Meta -analysis was performed using RevMan 5. 3 software after data extraction and bias risk assessment. Results:A total of 11 RCTs were included. Meta-analysis showed the efficacy of octreotide group was similar to that of somatostatin group (OR=1. 10, 95%CI:0. 79-1. 53, P=0. 56). The levels of blood transfu-sion and hemostasis of octreotide group were higher than those of somatostatin group (MD=0. 68, 95%CI:0. 54-0. 82, P<0. 01 and MD=6. 26, 95%CI:4. 89-7. 63, P<0. 01). The risk of abdominal pain in octreotide group was lower than that in somatostatin group (OR=0. 43, 95%CI:0. 22-0. 86, P=0. 02). The other adverse reactions were similar in both groups. Conclusion:The efficacy of octreotide is similar to that of somatostatin in the treatment of liver cirrhosis and upper digestive tract hemorrhage, and the effect of som-atostatin is quicker than that of octreotide with less blood transfusion. The adverse reactions are similar in both groups, except that oct-reotide has a lower risk of abdominal pain. The long-term safety of octreotide still needs to be confirmed by performing higher quality and large-sample RCTs.
3.Activation of the complement C3/C3aR pathway in the prefrontal cortex mediates methamphetamine addiction in rats
Fangmin WANG ; Shanshan CHEN ; Huizhen LIU ; Xiaolei HUANG ; Yiying ZHOU ; Manqing WU ; Miaojun LAI ; Dingding ZHUANG ; Huifen LIU ; Wenhua ZHOU
Chinese Journal of Pharmacology and Toxicology 2023;37(7):525-526
OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.
4.Research progress of pharmacological action and mechanism of piperine
Si LIN ; Huizhen QIN ; Lingyu DENG ; Miao ZHANG ; Fengfeng XIE ; Zeyu LI ; Hua ZHU
China Pharmacy 2022;33(13):1653-1659
Piperine is a kind of amide alkaloids presenting in Piper nigrum L.,which has the pharmacological action such as protecting cardiovascular system ,regulating glucose and lipid metabolism ,anti-tumor,improving nervous system diseases , anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ,as the main active ingredient of P. nigrum ,could protect the cardiovascular system by reducing inflammation and oxidative stress ;improve mitochondrial function through anti-inflammatory and antioxidant effects ,thereby regulate glucose and lipid metabolism ;play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin,NF-κB/Nrf-2/KeAP-1/HO-1, PI3K/Akt,TGF-β1/Smad2/ERK1/2;improve neurological diseases by inhibiting autophagy ,relieving inflammation ,improving antioxidant,inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ;play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However,the mechanism of action of piperine is not perfect ,and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ,without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ,the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.
5.Mechanism of Stemona tuberosa Alkaloids in Inhibiting Proliferation and Inducing Apoptosis of Non-small Cell Lung Cancer NCI-H460 Cells
Si LIN ; Huizhen QIN ; Liba XU ; Li LONG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):71-78
ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups (50, 100, 150, 200, and 250 mg·L-1). The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction (Real-time PCR) was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and epidermal growth factor receptor (EGFR). The protein expression levels of Caspase-3, Bax, Bcl-2, protein kinase B (Akt), phosphorylated (p-)Akt, EGFR, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group, the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation (P<0.01), reduced number of cell clones formed and the rate of cell clonal formation (P<0.05, P<0.01), and increased karyopyknosis, cytoplasmic aggregation, and cell apoptosis rate (P<0.01). The S. tuberosa alkaloids groups at 100, 150, 200, and 250 mg·L-1 showed increased Caspase-3 mRNA expression (P<0.05), decreased EGFR mRNA expression (P<0.05, P<0.01), up-regulated protein expression of Caspase-3 and p-JNK (P<0.01), and down-regulated protein expression of EGFR and p-Akt (P<0.05, P<0.01). Additionally, compared with the blank group, the S. tuberosa alkaloids groups showed increased expression of Bax mRNA (P<0.01), decreased expression of Bcl-2 mRNA (P<0.01), up-regulated protein expression of Bax and p-p38 MAPK (P<0.01), and down-regulated protein expression of Bcl-2 (P<0.01). ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells, and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein, as well as the activation of the JNK/p38 MAPK signaling pathway.
6.Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells
Si LIN ; Huizhen QIN ; Zeyu LI ; Liba XU ; Lingyu DENG ; Jing LUO ; Fengfeng XIE ; Miao ZHANG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):69-76
ObjectiveTo investigate the effect of Stemona tuberosa alkaloids (STA) on apoptosis and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups (100, 150, 200, 250, 300 mg⋅L-1). Thiazole blue (MTT) assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining, flow cytometry, and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Bcl-2, and the expression of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, JNK, p-JNK, p38 MAPK, and p-p38 MAPK. ResultCompared with the blank group, STA groups (150, 200, 250, 300 mg⋅L-1) demonstrated the increase in inhibition rate of cell proliferation (P<0.01) and cell clone inhibition rate, and decrease in cell clone formation rate (P<0.01). In comparison with the blank group, STA groups showed typical characteristics of apoptosis, such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group (P<0.01). Compared with the blank group, STA (150, 200, 250, 300 mg⋅L-1) significantly up-regulated the protein expression of Caspase-3 and Bax (P<0.05, P<0.01) and down-regulated the expression of Bcl-2 protein (P<0.01). Compared with the blank group, STA had no significant influence on the total protein expression of PI3K, Akt, JNK, and p38 MAPK. However, STA (150, 200, 250, 300 mg⋅L-1) significantly decreased the levels of p-PI3K and p-Akt (P<0.05, P<0.01) and increased the level of p-p38 MAPK (P<0.05, P<0.01). Compared with the blank group, STA (200, 250, 300 mg⋅L-1) significantly raised the level of p-JNK (P<0.05, P<0.01). ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.